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Biomedical subjects

T W van der Mark

Publications and source records attributed to T W van der Mark.

At least 19 recordsLinked to original sources
PubMed1998

Short-term treatment with budesonide does not improve hyperresponsiveness to adenosine 5'-monophosphate in COPD.

The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 microg budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC20AMP, PC20MCh, or FEV1 after placebo pretreatment. Budesonide increased PC20MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p = 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p < 0.001). We conclude that AMP did not elicit greater sensitivity than MCh in assessing short-term effects of budesonide on AHR in smokers with COPD. We suggest that long-term treatment with inhaled corticosteroids might be beneficial, by reducing neutrophil load in the airways and improving the action of anticholinergic drugs.

Adenosine Monophosphate↗
PubMed1997

Stereoselective synthesis and biodistribution of potent [11C]-labeled antagonists for positron emission tomography imaging of muscarinic receptors in the airways.

Quantitation of muscarinic receptors in the lungs in vivo with positron emission tomography (PET) is of clinical interest. For that purpose we decided to develop [11C]-labeled ligands with a high affinity (KD < 0.1 nM). Three quaternary muscarinic antagonists, racemic N-methylpiperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 1a (pKB = 10.39), its (R)-isomer 1b (pKB = 11.08), and (R,R)-quinuclidin-3-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide 2 (pKB = 11.28), were labeled by reacting [11C]CH3I with their tertiary amine precursors. The enantiomerically pure tertiary amine precursors were prepared by stereoselective synthesis starting from (R)-(-)-mandelic acid. In vitro binding assay of 1b and 2 demonstrated that both ligands bind with very high affinity to the muscarinic receptor subtypes M1, M2, and M3. They are more potent than the muscarinic antagonist (R)-N-methylquinuclidinyl benzilate ((R)-MQNB). Distribution studies with 1a, 1b, and 2 in control and atropine-treated male Wistar rats demonstrated significant specific binding (90-99% of total issue uptake) in tissues containing cholinoceptors (heart, intestine, lung, pancreas, spleen, stomach, submandibular gland). Because the tissue/plasma concentration ratios of 1b are most favorable, this ligand was used for further evaluation. Analysis of plasma samples showed a very rapid clearance (t1/2 = 0.3 min) of the radioligand 1b and a relatively slow appearance of a hydrophilic metabolite. At 15 min postinjection of 1b, analysis of heart, lungs, and liver showed that respectively 99%, 88%, and 8% of the tissue radioactivity corresponded with the parent compound. Ligand 1b appears to be an excellent candidate for PET studies of mAChR receptors in heart and lungs.

Animals↗
PubMed1997

Respiratory muscle activity and pulmonary function during acutely induced airways obstruction.

BACKGROUND: Patients with airway obstruction may spontaneously breathe with a positive expiratory pressure by pursing their lips during expiration, especially in case of dyspnea. Dyspnea seems to be related to increased activity of the respiratory muscles. A potential explanation for the use of pursed lips breathing (PLB) is that this type of breathing leads to a reduction of respiratory muscle activity. The purpose of this study was to assess the effect of breathing with a positive expiratory pressure of 5 cm H2O, simulating pursed lips breathing (SPLB), on respiratory muscle activity and pulmonary function during induced airway obstruction. METHODS: In twelve asthmatic patients, tonic and phasic electromyographic (EMG) activity of the following muscles was obtained: scalene muscle, parasternal muscle, and abdominal muscles. Pulmonary function and EMG measurements were performed before and after propranolol induced airway obstruction. RESULTS: Simulated pursed lips breathing resulted in a significant increase of functional residual capacity and tidal volume both at baseline and during airway obstruction. Phasic respiratory muscle activity during PEP breathing increased especially at baseline. We conclude that beneficial effects of breathing with a positive expiratory pressure of 5 cm H2O, which is similar to pursed lips breathing, cannot be explained by changes in respiratory muscle activity or pulmonary function.

Acute Disease↗
PubMed1997

Effects of hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan on pulmonary function assessments.

High doses of tumor necrosis factor-alpha (TNF) seem to be effective in the treatment of solid tumors in the extremities. By applying current intensive care technology, systemic administration of high doses of TNF levels might be feasible for the treatment of cancer in other localizations. To establish the early and late effects of high systemic TNF levels on the lungs, we determined lung function parameters in 12 patients before and after hyperthermic isolated limb perfusion (HILP) with TNF and melphalan. Because of leakage during perfusion, mean maximum systemic TNF levels of 60.0 ng/ml (range, 0.3-356 ng/ml) were obtained. Significant alterations in the vital capacity (VC), the capillary blood volume (Vc), the diffusing capacity of the alveolocapillary membrane (Dm), and the transfer capacity of the lungs for carbon monoxide per unit alveolar volume (KCO) were observed 1 week after HILP. Eight weeks after HILP, they returned to pretreatment value. Alterations in lung functions were not related to the maximum systemic TNF level. In conclusion, disturbances in pulmonary functions are observed in patients after HILP with TNF and melphalan. These disturbances, which are probably partly caused by high systemic TNF levels, are reversible and would not preclude administration of systemic TNF in high doses.

Adult↗
PubMed1997

Mini-Wright peak flow meters are reliable after 5 years use. Dutch CNSLD Study Group.

In studies with a long-term follow-up, peak expiratory flow (PEF) meters are often used to assess bronchial obstruction. The question arises whether data obtained with these frequently used meters are still reliable after several years of use, and whether the old meters should be renewed after a certain period. In the present study, we tested the reliability of PEF values measured with mini-Wright PEF meters that had been used frequently for 5 yrs. The values obtained with these meters were compared with values measured with identical but new meters, in 50 patients with obstructive airways disease. Though statistically significant, there was no clinically significant difference in mean PEF measured with the old and new meters in most patients (mean difference 10.2 L.min-1). However, on an individual basis, the differences between old and new meters could be large (upper and lower limits of agreement (mean +/- 2 SD) being 63.6 and -43.2 L.min-1, respectively). We conclude that mean peak expiratory flow values measured with frequently used mini-Wright peak expiratory flow meters are still reliable after 5 yrs. In long-term studies, renewal of peak expiratory flow meters should be restricted to cases of obvious malfunction.

Equipment Failure↗
PubMed1997

Water vapour and carbon dioxide decrease nitric oxide readings.

Measurement of nitric oxide levels in exhaled air is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process. The influence of these gases at the concentrations present in exhaled air, has not yet been studied. For this in vitro study, mixtures of 50, 100 and 200 parts per billion (ppb) NO in air were prepared and fed into the NO analyser either directly or bubbled through water. Mixtures with CO2 were prepared by adding 0-10% CO2 to the diluent air. We found a significant decrease in NO readings in the water-saturated samples compared to the dry gas (p < 0.001), strongly dependent on the partial pressure of water. NO levels in exhaled air (mean 10 +/- 2 ppb) showed a decrease of 17 +/- 3% when water vapour was not absorbed. From the experiments with CO2 we found a decrease in NO reading of 1.04 +/- 0.07% per volume CO2 (%). Presence of water vapour, thus, leads to a systematic underestimation of NO levels. Insertion of a water absorber might, therefore, be advantageous. The influence of CO2 concentrations in the normal respiratory range is negligible. With high expiratory CO2 levels as applied in permissive hypercapnia, the effects may be substantial.

Carbon Dioxide↗
PubMed1997

Characterization of pulmonary and myocardial beta-adrenoceptors with S-1'-[fluorine-18]fluorocarazolol.

UNLABELLED: S-1'-[18F]fluorocarazolol was administered to healthy volunteers to assess its potential for noninvasive measurement of regional pulmonary and myocardial beta-adrenoceptor densities. METHODS: High-specific activity fluorocarazolol was intravenously injected on two separate occasions within a 1-wk interval. The initial injection was without pretreatment, but before the second injection, the volunteers either inhaled salbutamol (2 x 200 micrograms aerosol) or they ingested pindolol (3 x 5 mg during a 12-hr interval). Twenty-eight PET time frames of 31 planes were acquired over a period of 60 min after each injection. Blood samples were drawn and analyzed for the presence of fluorocarazolol and radioactive metabolites. RESULTS: Uptake of fluorocarazolol in the target tissues was hardly affected by salbutamol but was strongly depressed by pindolol. Pulmonary and myocardial tissue-to-plasma concentration ratios of fluorocarazolol reached plateau values of 11.6 +/- 0.6 (lungs) and 18.1 +/- 1.0 (heart) at 45-50 min postinjection. These values were reduced to 2.0 +/- 0.4 and 2.0 +/- 0.6 after treatment with pindolol. CONCLUSION: These data indicate that: 1. Pulmonary and myocardial uptake of radioactivity after intravenous administration of S-1'-[18F]fluorocarazolol represents radioligand binding to beta-adrenoceptors. 2. Pulmonary binding occurs mainly in alveoli rather than in airway smooth muscle under these conditions. 3. Binding kinetics do not preclude quantification of receptors with compartment models.

Adrenergic beta-Agonists↗
PubMed1997

Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.

UNLABELLED: We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0, 5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. METHODS: The (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk. The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. RESULTS: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum. Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain. The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. CONCLUSION: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease.

Adrenergic beta-Antagonists↗
PubMed1996

Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatin.

We examined whether cisplatin-induced nephrotoxicity augmented bleomycin-induced pulmonary toxicity in patients with testicular cancer treated with etoposide and cisplatin with (BEP) or without bleomycin (EP). Before and at 3-week intervals during chemotherapy, creatinine clearance and lung functions were measured. In patients receiving BEP, deterioration of renal function correlated with a decrease in transfer factor of the lungs for carbon monoxide (TLCO) and vital capacity (VC), parameters known to reflect bleomycin-induced pulmonary effects. Other lung functions did not correlate with renal function. In the EP group, no relationships were observed at all. These observations suggest enhanced pulmonary effects of bleomycin when combined with cisplatin. Therefore, attention should be paid to the potential development of bleomycin-induced pulmonary toxicity in patients treated with BEP.

Adolescent↗
PubMed1996

Home assessment of peak inspiratory flow through the Turbohaler in asthmatic patients.

BACKGROUND: The efficacy of dry powder inhalers depends on the patient's inspiratory flow. Drug delivery from the Turbohaler (Turbuhaler in some countries), a multidose powder inhaler, is optimal at flows of > 40 l/min. The aim of this study was to investigate the peak inspiratory flow that can be generated by asthmatic patients through the budesonide Turbohaler (PIFTBH) during maintenance treatment at home. METHODS: Thirty asthmatic patients, consecutively recruited from the outpatient clinic, inhaled their maintenance dose of 800 (n = 16) or 1600 micrograms/day (n = 14) for two months or one month, respectively. The Turbohaler was connected to a modified Vitalograph Compact installed at home to obtain printed PIFTBH values for all inhalations. Peak expiratory flow (PEF) was measured twice daily. RESULTS: Flows were remarkably constant with individual mean PIFTBH values ranging from 55 l/min to 95 l/min. Only 13 of the 5248 PIFTBH recordings taken at home (three patients) were < 40 l/min and all were > 30 l/min. Weekly mean morning PEF values ranged from 114 l/min to 733 l/min. PIFTBH values could not be accurately predicted from lung function parameters in individual patients. CONCLUSIONS: In a group of stable asthmatic patients inspiratory flow rates rarely fell below the 40 l/min needed to operate a Turbohaler.

Adolescent↗
PubMed1996

Effects of cessation of terbutaline treatment on airway obstruction and responsiveness in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients with asthma may lead to a temporary deterioration of lung function and airway responsiveness. Few such studies have been reported in patients with chronic obstructive pulmonary disease (COPD), so an investigation was carried out to determine whether rebound airway responsiveness and rebound bronchoconstriction also occurs in COPD and if there is any relationship with the dose of beta 2 agonist being used. METHODS: Lung function (forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20 methacholine (PC20)) and symptoms were assessed in a double blind, placebo controlled crossover study during and after cessation of two weeks regular treatment with placebo, and low dose (250 micrograms) and high dose (1000 micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7 (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10, 14, 34 and 82 hours after the last inhalation of terbutaline or placebo. Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour values in each period, transformed into an area under the curve (AUC) value and analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during terbutaline treatment. PC20 and FEV1 did not change after cessation of terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low and high dose inhaled terbutaline does not result in a rebound bronchoconstriction and rebound airway responsiveness in patients with COPD.

Aged↗
PubMed1996

Rebound airway obstruction and responsiveness after cessation of terbutaline: effects of budesonide.

Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.

Administration, Inhalation↗
PubMed1996

Surfactant nebulization does not alter airflow obstruction and bronchial responsiveness to histamine in asthmatic children.

To test the hypothesis that surfactant nebulization improves pulmonary function and reduces bronchial responsiveness to histamine, we studied 12 children with asthma. We measured before and after inhalation of 100 mg nebulized natural-derived bovine surfactant (Alveofact (registered)) and after nebulization of 0.9% NaCl the change in peak expiratory flow, vital VC, FEV1, and forced expiratory flows at 50 and 75% of the flow-volume curve. In addition, we performed a histamine inhalation challenge. We did not find any significant changes in these parameters after nebulization of surfactant. These findings indicate that the inhalation of nebulized surfactant does not alter airflow obstruction and does not alter bronchial responsiveness to histamine in asthmatic children with airflow obstruction.

Adolescent↗
PubMed1996

Long-term effects of home rehabilitation on physical performance in chronic obstructive pulmonary disease.

A pilot study was set up to assess the long-term effects of once weekly versus once monthly follow-up of pulmonary rehabilitation after a comprehensive home rehabilitation program on physical performance in patients with chronic obstructive pulmonary disease (COPD) during an 18-mo period. Thirty-six patients with a mean FEV1 of 1.3 +/- 0.4 L (43% pred) were included in the study. Groups A and B (n = 23) visited the physical therapist twice weekly for 3 mo. Thereafter, 11 patients (Group A) had a follow-up of pulmonary rehabilitation once a week, and 12 patients (Group B) had a follow-up once a month. Thirteen patients received no rehabilitation at all (Group C). Long-term home rehabilitation does not appear to improve exercise tolerance; however, on the other hand, there is a deterioration in vital capacity (p < 0.01), walking distance (p < 0.01), and maximal work load (p < 0.05), as shown in the control group. A small improvement in exertional dyspnea (p < 0.01) after 18 mo and inspiratory muscle function (p < 0.05) after 12 mo was shown only in Group A. Because of the insufficient number of patients enrolled in this pilot study, no clear benefit on physical performance of long-term home rehabilitation with either weekly or monthly supervision could be demonstrated.

Exercise Test↗
PubMed1996

Effects of home rehabilitation on physical performance in patients with chronic obstructive pulmonary disease (COPD).

We investigated whether 12 weeks of rehabilitation at home in patients with chronic obstructive pulmonary disease (COPD) had a beneficial effect on lactate production, metabolic gas exchange data, workload of the inspiratory muscles, and dyspnoea during a maximal bicycle ergometer test. A second aim was to assess whether a change in dyspnoea was related to a change of inspiratory muscle workload. Forty three COPD patients with severe airways obstruction were included in the study: mean forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 L (44% predicted), mean FEV1/inspiratory vital capacity (IVC) 37 +/- 8%. Twenty eight patients started a rehabilitation programme, whilst 15 patients received no rehabilitation. Rehabilitation was carried out at home; patients were supervised by a general practitioner, a physiotherapist and a nurse. Exercise tolerance was measured by means of a 6 min walking distance test (6MWD) and maximal workload (Wmax) during an incremental symptom-limited cycle ergometer test. Inspiratory muscle workload at Wmax was assessed with the Tension Time Index (TTI), and dyspnoea at Wmax with the Borg scale. After 12 weeks, the rehabilitation group showed a significantly larger increase in 6MWD (from 438 to 447 m) and in Wmax (from 70 to 78 W) compared with the control group. A significant improvement in oxygen consumption (V1O2) (from 1.0 to 1.1 L), lactate level (from 3.7 to 3.1 mEq.L(-1)), dyspnoea (from 6.0 to 4.5) and TTI (from 0.10 to 0.08) at Wmax occurred in the rehabilitation group during the programme. The reduction in TTI was not significantly correlated with the fall in dyspnoea, as assessed by the Borg scale. We conclude that 12 weeks of rehabilitation at home in COPD patients increases symptom-limited V1O2 in combination with an increased Wmax. At this significantly higher Wmax, there was a reduction in dyspnoea, lactate level and inspiratory muscle workload. The reduction in dyspnoea was not related to a decreased inspiratory muscle workload. This study shows that rehabilitation at home can produce beneficial physiological improvements during exercise in patients with chronic obstructive pulmonary disease.

Aged↗
PubMed1995

Decrease in pulmonary function during bleomycin-containing combination chemotherapy for testicular cancer: not only a bleomycin effect.

This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This enabled us to establish whether effects other than those due to bleomycin determined the detrimental effects of BEP on lung function assessments. Slow inspiratory vital capacity (VC), the transfer factor of the lungs for carbon monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm), the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs for carbon monoxide per unit alveolar volume (KCO) were determined before and at 3 week intervals during chemotherapy. Both groups, similar in terms of factors that may influence pulmonary function, showed during therapy a significant decrease in TLCO compared with the pretreatment value. Only at the end of the therapy was a significant difference in TLCO between both groups observed. Dm diminished also significantly in both groups during treatment, but differences between both groups were not seen. VC and Vc decreased in patients receiving BEP but remained constant during treatment with EP. It can be concluded that the Dm, KCO, and the widely used TLCO are not suitable parameters to monitor specifically pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However, VC and Vc appear to be proper lung function assessments which reflect specifically alterations induced by bleomycin.

Adolescent↗
PubMed1995

Pulmonary function changes in lung-cancer patients treated with radiation with or without carboplatin.

In order to examine changes in pulmonary function in patients with locally advanced non-small-cell lung cancer (NSCLC) before, during, and after standard radiotherapy or combined chemoradiotherapy, we conducted a prospective study involving patients with such cancer, who were treated with radiation alone or with concurrent radiation and carboplatin from October 1992 to February 1994 at the University Hospital in Groningen, the Netherlands. Thirty-five patients were treated. Two patients were excluded because of pulmonary emphysema. Pretreatment values of TLC, VC, the gas-transfer coefficient (Kco), the pulmonary diffusing membrane factor (Dm), and pulmonary capillary blood volume (Vcap) were lower than in normal subjects and patients with chemotherapy-naive germ-cell carcinoma who had a similar pulmonary tumor load as the result of hematogenous metastases. The NSCLC patients' reduced Kco was explained by a decrease in Dm, a measure of alveolar-capillary membrane disturbance, and a similar decrease in Vcap. Pretreatment TLC did not correlate with Vcap or Dm, indicating extra- rather than intrapulmonary vascular and lymphatic obstruction as an explanation for the reduced Vcap and Dm. Locally advanced NSCLC was treated with radiation (n = 16) or combined continuous carboplatin infusion and radiation (n = 17). No changes in TLC, VC, Kco, Dm, or Vcap were observed during and 2 wk after the end of either treatment, nor were any differences in pulmonary function observed with the two treatments, indicating an absence of additional acute pulmonary toxicity caused by continuously infused carboplatin in this patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗